Yale University

Unigene Laboratories Inc.

Boehringer Ingelheim International Gmbh

Kieran Murphy LLC

Agnès Vignery

Nozer M Mehta

James P Gilligan

Kieran Murphy

Jun Li

Compositions and methods are provided for modulating cell-cell fusion by using agents that modulate expression, activity, or function of intermediate-conductance calcium-activated potassium (SK4) channel. In some embodiments, the compositions and methods of the invention provide for inhibition of multi-nucleated osteoclastogenesis and cell-cell fusion, especially cell fusion involving macrophages. In such embodiments, the compositions can comprise inhibitory nucleic acids, monoclonal antibodies or small molecule inhibitors of the SK4 channels and find use in preventing and/or treating various diseases or disorders including bone loss, autoimmune and inflammatory diseases or disorders, implant and transplant rejection, and cancer metastasis. In other embodiments, the compositions and methods of the invention provide for activation of cell-cell fusion. Also provided are methods to screen for SK4 channel modulators (inhibitors or activators) that modulate cell-cell fusion, particularly macrophage cell fusion.

Compositions and methods for modulating cell-cell fusion via intermediate-conductance calcium-activated potassium channels

A method for augmenting bone in a subject in need thereof including installing within an interior portion of a bone located in the subject a sufficient amount of a biocompatible material to form a scaffold within the bone interior, wherein the scaffold serves as a support for the formation of new bone within the bone interior portion, and administering to the subject a sufficient amount of at least one bone augmentation agent to elevate blood concentration of at least one anabolic agent in the subject. The method may further include administering at least one anti-resorptive agent to the subject in an amount sufficient to substantially prevent resorption of new bone growth. In another embodiment, the method may further include a step of mechanically inducing an increase in osteoblast activity in the subject, wherein the elevation in blood concentration of the anabolic agent and the increase in osteoblast activity at least partially overlap in time.

Methods and compositions for fostering and preserving bone growth

A method of inducing bone formation in a subject in need of such inducement comprises the steps of mechanically inducing an increase in osteoblast activity in the subject and elevating blood concentration of at least one bone anabolic agent in the subject. The method steps may be performed in any order, but in sufficient time proximity that the elevated concentration of the anabolic agent and the mechanically induced increase in osteoblast activity overlaps. The method may additionally comprise providing the subject with an elevated blood concentration of at least one antiresorptive agent, wherein the elevated concentration is sufficient to prevent resorption of new bone growth produced due to the osteoblast activity. Use of the method permits targeting of specific bones of the subject for bone production and preservation, faster bone production and earlier discontinuation of bone anabolic pharmaceuticals. Kits adapted for performing the method are provided.

Method for fostering bone formation and preservation

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Branford, CT, United States of America

Agnès Vignery